Elsevier

Vaccine

Volume 26, Issues 29–30, 4 July 2008, Pages 3765-3771
Vaccine

Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000–2005

https://doi.org/10.1016/j.vaccine.2008.04.040Get rights and content

Abstract

In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases were registered annually during the period. The overall incidence of IPD increased significantly, from 15.4 cases per 100,000 population in 2000 to 20.7 cases per 100,000 in 2005 (p < 0.01), mainly due to an increase in bacteraemia cases. The serotype coverage in children under 5 years varied from 64% to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually by introducing a PCV. Approximately 70% of all deaths occurred in adults over 65 years, underlining the need for protection against IPD in this age group.

Introduction

Severe pneumococcal disease is the number one vaccine-preventable cause of death in children younger than 5 years of age worldwide and is an important cause of morbidity and mortality in both developing and industrialized countries [1]. The most severe form of invasive pneumococcal disease (IPD), pneumococcal meningitis, has become the most frequent aetiology of bacterial meningitis throughout the last decade in Denmark [2], [3] with the highest incidence among children younger than 2 years and among the elderly. Further attention to pneumococcal disease has been drawn worldwide after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) in the childhood immunization programme in the United States in 2000.

PCV7 has shown to be highly effective in preventing IPD caused by vaccine-serotypes (IPD-VT) in children [4], [5]. A protective effect, or herd protection, has been observed in older cohorts as well [6], [7]. Additionally, a recent study has shown a decline in the number of patients hospitalized with pneumonia and specifically pneumococcal pneumonia [8]. Several European countries have introduced PCV7 in their national childhood immunization programmes [9]. PCV7 was introduced in the Danish childhood immunization programme in October 2007, and it is administrated free of charge to children at the age of 3, 5, and 12 months, simultaneously with the other vaccines [10]. Previously, vaccination with PCV7 was only recommended for children belonging to high risk groups, including children with spleen dysfunction, immunodeficiency, former IPD, cerebrospinal fluid (CSF) leaks or chronic heart or lung diseases.

Differences in blood culture practices and surveillance systems may influence the detection and reporting rates of IPD, making it difficult to compare estimations on burden of disease in European countries [11], [12]. In Denmark, national surveillance of IPD has remained practically unchanged throughout the last decades [13]. The aim of the present study was to describe the epidemiology of IPD during the years 2000–2005, including the mortality associated with the disease, and to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV).

Section snippets

IPD-surveillance

The characteristics of the national surveillance system for IPD have previously been described [11]. Laboratory surveillance of IPD is based on voluntary submission of S. pneumoniae isolates cultured from a normal sterile site from all local departments of clinical microbiology to the National Neisseria and Streptococcus Reference Center (NSR), Statens Serum Institut. In 2004 and 2005, the NSR laboratory received between 96% and 100% of all S. pneumoniae isolates obtained from CSF or blood

Frequencies and incidence rates

The total number of IPD cases reported to the NSR Center during the study period was 6478 cases among 6333 patients (51% females), with an average of 1080 cases per year. Two per cent of the total number of patients (n = 129) had a recurrent IPD case. Bacteraemia cases accounted for 91% of the total (n = 5917) and meningitis accounted for 8% (n = 517). Less than 1% (n = 44) of pneumococcal isolates were recovered from other sterile sites. Eight per cent of IPD cases (n = 511) were obtained from children

Discussion

Estimation of the potential impact of PCV7 has become a priority in several countries following the positive experiences from the United States where PCV7 was introduced to the recommended vaccination schedule in 2000. The present study showed that in Denmark the serotype coverage of the current and forthcoming conjugate vaccines is similar to what has been reported from other European countries [29]. Our results also suggest that the estimated burden of IPD in terms of mortality is

Acknowledgements

We acknowledge the Departments of Clinical Microbiology in Denmark for submitting invasive pneumococcal isolates for national surveillance. We acknowledge the staff performing the serotyping of the isolates and entering the data at the NSR Center during the study period. We also thank Kåre Mølbak, Head of the Department of Epidemiology, Statens Serum Institut for critical review of the manuscript and statistical advice. The results reported in this study were partially presented at the 17th

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